PPAR(alpha) and PPAR(gamma) activators suppress the monocyte-macrophage apoB-48 receptor

Certain triglyceride-rich lipoproteins (TRLs), specifically chylomicrons, dyslipemic VLDLs, and their remnants, are atherogenic and can induce monocyte-macrophage foam cell formation in vitro via the apolipoprotein B-48 receptor (apoB-48R). Human atherosclerotic lesion foam cells express the apoB-48R, as determined immunohistochemically, suggesting it can play a role in the conversion of macrophages into foam cells in vivo. The regulation of the apoB-48R in monocyte-macrophages is not fully understood, albeit previous studies indicated that cellular sterol levels and state of differentiation do not affect apoB-48R expression. Since peroxisome proliferator-activated receptors (PPARs) regulate some aspects of cellular lipid metabolism and may be protective in atherogenesis by up-regulation of liver X-activated receptor alpha and ATP-binding cassette transporter A1, we examined the regulation of apoB-48R by PPAR ligands in human monocyte-macrophages. Using real-time PCR, Northern, Western, and functional cellular lipid accumulation assays, we show that PPARalpha and PPARgamma activators significantly suppress the expression of apoB-48R mRNA in human THP-1 and blood-borne monocyte-macrophages. Moreover, PPAR activators inhibit the expression of the apoB-48R protein and, notably, the apoB-48R-mediated lipid accumulation of TRL by THP-1 monocytes in vitro. If PPAR activators also suppress the apoB-48R pathway in vivo, diminished apoB-48R-mediated monocyte-macrophage lipid accumulation may be yet another antiatherogenic effect of the action of PPAR ligands.     

Introduction of short interfering RNA to silence endogenous E-selectin in vascular endothelium leads to successful inhibition of leukocyte adhesion

Short interfering RNAs (siRNAs) are powerful sequence-specific reagents that suppress gene expression in mammalian cells. We report for the first time that gene silencing of endothelial E-selectin by siRNAs leads to successful inhibition of leukocyte-endothelial interaction under flow. siRNAs designed to target human E-selectin were tranfected into human umbilical vein endothelial cells (HUVEC). Western blotting analysis revealed that transfection of these siRNAs, but not the scrambled control siRNA (100nM each), attenuated E-selectin expression in HUVEC activated with TNF-alpha (10ng/ml, 4h) without affecting expression of ICAM-1. Moreover, a leukocyte adhesion assay under flow (shear stress=1.0dyne/cm(2)) demonstrated that HUVEC transfected with a siRNA against E-selectin (siE-01) supported significantly less HL60 adhesion as compared to those transfected with the control siRNA (scE-01) after activation (p<0.03). This technique provides a powerful strategy to dissect a specific function of a given molecule in leukocyte-endothelial interaction.     

Enzyme Aided Regioselective Acylation of Nucleosides

Abstract

Selective protection of the three hydroxyl groups of sugar moiety of nucleosides have been studied by enzyme-catalyzed esterification in organic solvents. Selectively protected products were obtained. The reaction provides an efficient method for selective protection of nucleosides.     

A Facile Preparation of Dehydro-l-ascorbic Acid-methanol Solution and Its Stability

A papain-catalyzed reaction involving the covalent attachment of L-leucine ra-dodecyl ester [Agric. Biol. Chem., 44, 1979 (1980)] was applied to gelatin and succinylated fish protein concentrate. Proteinaceous surfactants formed were found suitable for emulsification of soybean oil. The emulsions prepared with these surfactants were characterized by having a variety of functional properties in terms of hardness, adhesiveness, viscosity and viscoelasticity. Any particular property could be reproduced by intentionally setting the proper conditions for emulsification; for example, the use of a high surfactant concentration resulted in gel formation. The functions of the proteinaceous surfactants were different in many respects from those of Tween-60 and a type of sucrose fatty acid ester used as controls. Several data were added explaining such differences. The feasibility of preparing a mayonnaise-like concentrated emulsion by use of the proteinaceous surfactants is discussed.     

The dose response of chromosome aberrations in human lymphocytes induced in vitro by very low-dose γ rays

This paper considers the dose-effect relationship for unstable chromosome aberration yields in human lymphocytes in very low-dose range. Data are presented for (60)Co γ-ray doses of 0, 10, 20, 40 and 1000 mGy. More than 5,000 metaphases were scored for each data point at the very low doses, and each cell was double-checked using a semi-automated metaphase finding/relocation system. Aberration yields of dicentrics plus centric rings followed an excellent linear dose response down to zero dose; the yields were significantly above the control frequency from 20 mGy.